Most risk factors for male breast cancer have been derived from retrospective studies that may reflect selective recall. In the prospective National Institutes of Health-AARP Diet and Health Study, we studied 324 920 men, among whom 121 developed breast cancer. Men who reported a first-degree relative with breast cancer had an increased risk of breast cancer (relative risk [RR] = 1.92, 95% confidence interval [CI] = 1.19 to 3.09). Among the medical conditions examined, a new finding emerged regarding increased male breast cancer risk associated with a history of a bone fracture (RR = 2.20, 95% CI = 1.24 to 3.91). Obesity was positively related to risk (RR = 1.79, 95% CI = 1.10 to 2.91, for body mass indices of >or=30 vs <25 kg/m2) and physical activity inversely related, even after adjustment for body mass index. Smokers were at somewhat elevated risk, although trends with smoking characteristics were inconsistent. Alcohol consumption was not related to risk. The identified risk factors show some commonalities with female breast cancer and indicate the importance of hormonal mechanisms. Differences in risk factors may reflect unique mechanisms associated with androgens and their ratio to bioavailable estrogens.